The Society of Thoracic Surgeons Practice Guideline Series ... - STS

REPORT FROM THE WORKFORCE ON EVIDENCE-BASED MEDICINE

The Society of Thoracic Surgeons Practice

Guideline Series: Antibiotic Prophylaxis in

Cardiac Surgery, Part II: Antibiotic Choice*

Richard Engelman, MD, David Shahian, MD, Richard Shemin, MD,

T. Sloane Guy, MD, Dale Bratzler, DO, MPH, Fred Edwards, MD,

Marshall Jacobs, MD, Hiran Fernando, MD, and Charles Bridges, MD, ScD

I. Overview

The importance of prophylactic antibiotics for cardiac

surgery has been clearly demonstrated in a number of

placebo-controlled studies completed nearly 30 years ago

[1�C 4]. Surgical site infections (SSIs) and particularly sternal and mediastinal infections have implications for

significantly increasing both morbidity and mortality, as

well as their associated costs in both man-hours and

dollars spent [5, 6].

Part I of this evidence-based guideline series (The

Society of Thoracic Surgeons Practice Guideline Series: Antibiotic Prophylaxis in Cardiac Surgery, Part I: Duration, published in the January 2006 issue of the Annals of Thoracic

Surgery) recommended that the duration for routine postoperative administration of prophylactic antibiotics be no

longer than 48 hours [7]. This initial Guideline did not

define the choice of antibiotic to be recommended, its

dose, or frequency of administration. Those subjects are

the basis for this report.

II. Choice of Primary Prophylactic Antibiotic

Cephalosporin or Glycopeptide

CLASS I RECOMMENDATION. A ?-lactam antibiotic is indicated

as a single antibiotic of choice for standard cardiac

surgical prophylaxis in populations that do not have a

high incidence of methicillin-resistant Staphylococcus

aureus (MRSA [Level of Evidence A; see Appendix]).

There are numerous publications concerned with the

optimal prophylactic antibiotic recommended for cardiac

surgery, but many of these protocols are comparing not

only two or more antibiotic regimens but also two different dosing programs, for example, single dose versus

multidose, which was addressed in the previous Guideline. This second published Guideline will address addi-

*For the full text of the STS Guideline on Antibiotic Prophylaxis in

Cardiac Surgery, as well as other titles in the STS Practice Guideline

Series, visit

practiceguidelines/ at the official STS website ().

Address correspondence to Dr Engelman, Baystate Medical Center,

Division of Cardiac Surgery, 759 Chestnut St, Springfield, MA 01199;

e-mail: richard.engelman@.

? 2007 by The Society of Thoracic Surgeons

Published by Elsevier Inc

tional publications in so far as they compare different

antibiotic regimens involving comparable duration of

multidose antibiotic administration.

The most pertinent report appeared in 2004 [8] and was

a very complete meta-analysis of seven randomized

trials, comparing the incidence of SSIs in patients receiving either glycopeptide prophylaxis (vancomycin or

teicoplanin) or a ?-lactam. Five of the seven trials used a

multidose regimen and two invoked, in one of their trial

groups, the single preoperative administration of a longacting agent. In both of these latter reports, the singledose agent was either less effective or not significantly

different from the multidose antibiotic [9, 10]. In this

international, multi-institutional meta-analysis involving

5,761 patients, ?-lactams were at least as effective as

glycopeptides for the overall prevention of SSIs. However, only one institution defined their site as having a

high incidence of MRSA (more than 2.5 new cases of

MRSA infection or colonization per 100 admissions) [11],

and that may limit the degree to which these findings can

be generalized to current practice in which MRSA is

much more prevalent. Notwithstanding this caveat, it

appeared that prophylaxis with glycopeptides such as

vancomycin was less effective in preventing infection by

methicillin-sensitive organisms, while such prophylaxis

was more effective in preventing infection by methicillinresistant organisms [8].

Distinguishing Between Cephalosporins

Based on availability and cost,

it is reasonable to use cefazolin (a first-generation agent)

as the cephalosporin for standard cardiac surgical prophylaxis in view of the fact that most randomized trials

could not discriminate between cephalosporins (Level of

Evidence B).

The next issue to be addressed concerns the choice of

a ?-lactam, remembering that there are first- through

fourth-generation agents presently available, which have

differing half-lives, pharmacodynamics, and pharmacokinetics. It can be stated as fact that the later generation

cephalosporins have better gram-negative and less

gram-positive coverage. In that our predominant organism for cardiac surgical infections is a Staphylococcus sp,

CLASS IIA RECOMMENDATION.

Ann Thorac Surg 2007;83:1569 �C76 ? 0003-4975/07/$32.00

doi:10.1016/j.athoracsur.2006.09.046

MISCELLANEOUS

Baystate Medical Center, Springfield, Massachusetts; Tufts University School of Medicine, Boston, Massachusetts; Boston Medical

Center, Boston, Massachusetts; University of California, San Francisco, California; Oklahoma Foundation for Medical Quality,

Oklahoma City, Oklahoma; University of Florida, Shands Jacksonville, Jacksonville, Florida; St. Christopher��s Hospital for

Children, Philadelphia, Pennsylvania; and University of Pennsylvania Medical Center, Philadelphia, Pennsylvania

1570

WORKFORCE REPORT

ENGELMAN ET AL

ANTIBIOTIC PROPHYLAXIS IN CARDIAC SURGERY

the earlier generation cephalosporins are likely to be

preferred for prophylaxis. In fact, published data would

support that conclusion [12].

In 1987, a randomized trial of more than 1,000 cardiac

surgical patients was reported comparing multidose cefazolin, a first-generation cephalosporin, with multidose

cefamandole, a second-generation cephalosporin, and

found cefamandole to have a lower sternal infection rate

[13]. This study, however, introduced a second agent,

gentamicin, as an additional single-dose prophylactic

drug, in half the patients in each cephalosporin group.

That led to the comparative analysis being less than clear

cut in defining an optimal cephalosporin. A more definitive randomized double-blind study comparing individual cephalosporins in 1,641 patients from Johns Hopkins

Hospital between 1987 and 1990 was reported in 1993

[14]. The incidence of all surgical site infections was 8.4%

with cefamandole prophylaxis, 8.4% cefazolin, and 9.0%

with cefuroxime (clearly not significant). The relative

incidence comparing cephalosporins and differentiating

between deep and superficial infection was also not

significantly different between the groups (specifically,

deep sternal infection ? 0.6% cefamandole, 1% cefazolin,

and 1.5% cefuroxime). A 1992 meta-analysis [15] cited in

the Hopkins report includes some with inherent flaws

but still supports the conclusion that there is no cephalosporin regimen that is clearly superior in affecting a

lower infection rate.

MISCELLANEOUS

III. Issues Surrounding Staphylococcal Infection

Reasons for Concern in Cardiac Surgical Patients

Surgical site infections of the sternal wound and underlying mediastinum occur in 0.4% to 4% of cardiac surgical

procedures, with more than 50% due to S aureus or

coagulase-negative S epidermidis [16 �C22]. These infections

have profound short- and long-term implications. Inhospital mortality rates of 10% to more than 20% have

commonly been reported, and a 10-year follow-up study

of such patients by the Northern New England Cardiovascular Disease Study Group demonstrated a marked

negative impact not only on acute but also on long-term

survival [23]. Hollenbeak and colleagues [24] found a

1-year mortality rate of 22% for coronary artery bypass

graft surgery (CABG) patients with deep chest surgical

site infections versus 0.6% for uninfected patients (p ?

0.0001). Deep chest infection resulted in 20 additional

hospital days per patient (p ? 0.0001) and added an

average of $18,938 in hospital costs. Patients who died as

a result of their infection incurred average costs that were

$60,547 more than infected patients who lived.

The choice of a prophylactic antibiotic has become

increasingly controversial with the emergence of MRSA

and methicillin-resistant coagulase-negative Staphylococcus

(MRCNS). According to the National Nosocomial Infection Surveillance System Report, the median percentage

of MRSA isolates from intensive care unit (ICU) and

non-ICU patients in hospitals surveyed exceeded 40%,

and the median percentage of MRCNS isolates exceeded

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2007;83:1569 �C76

65% [25]. It has been estimated that colonization with

methicillin-resistant organisms, often asymptomatic, occurs in 4% to 8% of ICU patients, 0.18% to 7.2% of

inpatients, and 1.3% to 2% of persons in the community

[26]. In one urban hospital, the incidence of MRSA

among newly admitted patients was 7.3%, which is

higher than the 1.3% to 5.3% prevalence in previous

reports [27]. This alarming incidence of colonization has

led to a strong recommendation for active surveillance at

the time of hospital admission [27, 28]. At least one third

of MRSA-colonized patients will have a healthcarerelated MRSA infection, which is nearly 10 times the risk

of noncolonized patients [26, 28]. In a study by Lin and

associates [19] at a hospital with a high incidence of

MRSA, 65% of post-sternotomy staphylococcal infections

were due to methicillin-resistant organisms [19].

Some studies suggest that patients with poststernotomy MRSA/MRCNS infections have a less favorable prognosis compared with those having methicillinsensitive (MSSA) organisms. For example, in the study of

Mekontso-Dessap and colleagues [22], overall mortality

was 53.3% for MRSA post-sternotomy infections versus

19.2% for MSSA infections, with corresponding 3-year

actuarial survival rates of 26% versus 79%. Methicillinresistant S aureus was the only independent predictor of

overall mortality, and MRSA infections had a higher

incidence of mediastinitis-related death and treatment

failure compared with MSSA. In a study of SSIs composed

of largely cardiac and orthopedic procedures, Engemann

and associates [5] found a mortality rate of 20.7% for MRSA

versus 6.7% for MSSA, and most deaths in the cardiac

group were due to post-sternotomy mediastinitis. The costs

directly attributable to methicillin resistance were $13,901

per case of staphylococcal infection.

Potential (Nonallergic) Indications for Primary or

Adjuvant Glycopeptide (Vancomycin) Prophylaxis

In the setting of either a presumed or known staphylococcal colonization, the institutional presence of a ��high incidence�� of MRSA, patients

susceptible to colonization (hospitalized longer than 3

days, transfer from other inpatient facility, already receiving antibiotics), or an operation for a patient having

prosthetic valve or vascular graft insertion, it would be

reasonable to combine the ?-lactam (cefazolin) with a

glycopeptide (vancomycin) for prophylaxis, with the restriction to limit vancomycin to only one or two doses

(Level of Evidence C).

The progressive emergence of methicillin-resistant

staphylococcal organisms within hospitals and the community, as well as the possibly more serious course of

such infections in the cardiac surgery patient, has led

some to recommend more aggressive use of prophylactic

vancomycin, even for patients with no history of penicillin or cephalosporin allergy [29]. For example, it is argued

that patients having surgery in institutions with a high

incidence of methicillin resistance would be better

served by receiving vancomycin, although it is unclear as

to what constitutes a high incidence [6, 30]. Other potential candidates for vancomycin prophylaxis might include

CLASS IIB RECOMMENDATION.

patients who are at higher risk for preoperative MRSA

colonization, patients at higher risk for post-sternotomy

infection in general, and patients with specific risk factors

for MRSA post-sternotomy infection [31]. Active surveillance of admitted patients for staphylococcal colonization

is desirable [28, 32], but results for cardiac surgery

patients would generally not be available at the time of

surgery except in those institutions where rapid polymerase chain reaction (PCR) testing is available. Finally, it

has been suggested, but not generally accepted, that

because of the devastating consequences of prosthetic

valve or vascular graft infection with methicillin-resistant

organisms, these patients should also routinely receive

vancomycin [12, 29].

There are observational [33] and randomized trial data

[12] supporting the use of vancomycin prophylaxis for

cardiac surgery, as well as the results of a sophisticated

decision analytic model [6]. Using the best available

clinical and microbiological data from the literature,

Zanetti and colleagues [6, 30] estimated that routine

vancomycin use in a cohort of 10,000 CABG patients

would result in 29 fewer deep chest infections, 58 fewer

superficial infections, 3 fewer deaths, lower direct medical costs over 3 months, and a net $1,170,000 cost saving

compared with routine cefazolin. Sensitivity analysis

indicated that cephazolin was more effective or less costly

only when MRSA represented fewer than 3% of all

staphylococcal isolates in a hospital, which would be

unusual in contemporary practice. Based on 366,000

CABG procedures annually in the United States, this

model predicts that vancomycin use would result in 110

fewer deaths, prevent 3,184 SSIs, and potentially save $43

million.

One of the most serious objections to increased use of

vancomycin prophylaxis is concern about the emergence

of resistant strains of Staphylococcus and Enterococcus

organisms [34, 35]. This consideration has prompted the

publication of restrictive guidelines for the use of vancomycin or teicoplanin (both glycopeptides), which include

a specific recommendation by the CDC against the routine use of vancomycin for prophylaxis (36). However, it

should be noted that antibiotic resistance may also develop with ?-lactam antimicrobials. Furthermore, the

duration of vancomycin administration as a primary or

adjuvant prophylactic agent, as opposed to its use for

established post-sternotomy infections, must also be considered. In terms of the emergence of drug-resistant

organisms, which is worse�� using short-duration prophylactic vancomycin in a larger number of patients,

possibly preventing some clinical infections due to methicillin-resistant organisms; or using a cephalosporin

after which a serious SSI is more likely to involve MRSA

or MRCNS, thus committing such patients to weeks or

months of continuous vancomycin therapy [6, 29, 30]?

This is a central question that as yet has not been

resolved and would require research not likely to be

performed. Thus, this particular question cannot be addressed by randomized trials.

Unless there is demonstrated penicillin or ?-lactam

allergy (see Section V, ��Allergy to Penicillin��), it would

WORKFORCE REPORT

ENGELMAN ET AL

ANTIBIOTIC PROPHYLAXIS IN CARDIAC SURGERY

1571

appear most reasonable to employ a cephalosporin as the

primary prophylactic agent for the usual 24 to 48 hours,

and only to use vancomycin selectively as an adjuvant

agent, typically a single dose preoperatively (together

with the first dose of cephalosporin) with at most one

additional dose in valve or vascular implant patients or in

all patients in highly selected environments (eg, where

MRSA colonization is likely or documented or where

there is a high prevalence of MRSA isolates from infections). This should provide a reasonable compromise

between the goal of providing the broadest spectrum

prophylaxis at the time when it is likely to be most

effective, and the competing desire to restrict usage of

vancomycin in order to minimize the emergence of

resistant organisms.

Vancomycin as the Sole Prophylactic Antibiotic

Because vancomycin is an

agent that has no effect on gram-negative flora, its usefulness as an exclusive agent in cardiac surgical prophylaxis is not recommended (Level of Evidence C).

DISCUSSION. For situations in which vancomycin is believed to be indicated as prophylaxis for cardiac surgery,

for example, ?-lactam allergy, should it be used as a

single agent or combined with another antimicrobial?

Overall, vancomycin has a narrower antimicrobial spectrum, inferior tissue and bone penetration, less desirable

pharmacokinetics, and slower bactericidal killing compared with cephalosporins [5, 8, 16, 30, 37]; and the

incidence of SSI due to methicillin-sensitive organisms

has been higher when only vancomycin has been employed for prophylaxis [8, 11]. Additionally, since some

hospitals report both deep surgical site infections and

blood stream infections after cardiac surgery from gramnegative organisms [38], it is recommended that an

aminoglycoside be added for one preoperative and at

most one additional postoperative dose to act as a specific gram-negative agent when vancomycin is indicated

to be the primary prophylactic agent.

CLASS IIB RECOMMENDATION.

Mupirocin for Preoperative Therapy to Eliminate

Staphylococcal Nasal Colonization

Routine mupirocin administration is recommended for all patients undergoing cardiac

surgical procedures in the absence of a documented

negative testing for staphylococcal colonization (Level of

Evidence A).

DISCUSSION. Mupirocin is a patient self-administered topical antibiotic that is highly effective in eradicating nasal

S aureus, including methicillin-resistant strains of Staphyloccocus. It is a naturally occurring antibiotic produced by

a fermentation of Pseudomonas bacteria mixed in a nonirritating paraffin composition. Its specific mechanism of

action is to bind to isoleucyl-transfer RNA synthetase

and disrupt cell function [39]. It is reportedly more than

90% effective in eradicating nasal colonization of Staphylococcus for as long as 1 year [40]. Short-term therapy (a

5-day course) has been shown to be highly effective [41].

Correlation of nasal or hand colonization and infection in

the same patient by the same phage type of Staphyloccocus

CLASS I RECOMMENDATION.

MISCELLANEOUS

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2007;83:1569 �C76

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ENGELMAN ET AL

ANTIBIOTIC PROPHYLAXIS IN CARDIAC SURGERY

MISCELLANEOUS

has been shown to be near 90% [42]. Recent reports of

both randomized and nonrandomized trials in cardiac

surgical patients, one a meta-analysis, supports its routine use in prophylaxis [43�C 45].

Resistance to mupirocin ointment has become a concern for infectious disease specialists, but such resistance

is largely found after prolonged treatment periods when

used to treat either large open wounds or dermatitis.

There have been no reports of high-level drug resistant

strains developing after a short course of treatment such

as proposed for preoperative prophylaxis despite 4 years

of surveillance in one hospital using this approach routinely in both orthopedic and vascular surgery [46]. In

fact, many, if not most, cardiac surgical programs have

instituted a routine protocol for intranasal mupirocin

beginning at least the day before operation (sooner, if

elective operation) and continuing for 2 to 5 days after

surgery. Recently, a PCR rapid analysis for Staphyloccocus

sp has become available in some hospitals, with additional institutions gaining access to the technology on a

regular basis. A report has just been published [47] for a

PCR-based mupirocin study performed at the Cleveland

Clinic. In this study, screening for nasal carriage of S

aureus (both MRSA and MSSA) was routinely performed

before cardiac surgery. There were 6,334 patients

screened over 21 months, and 1,342 were found to have

colonization (21%), which is the identical incidence reported in a second study as well [45]. The administration

of mupirocin was reserved for these colonized patients,

and while the mupirocin use in the cardiac surgical

population declined significantly (by nearly 80%), there

was no demonstrable difference between carriers and

noncarriers in the overall incidence of infection or in the

incidence of infection caused by S aureus. It was concluded that the effect of mupirocin on colonized patients

resulted in appropriately reducing the Staphyloccal infection incidence to nullify the influence of colonization.

Because, inherently, one would not recommend use of

any agent that is not useful for treatment, limiting mupirocin prophylaxis to colonized patients would appear to

be a sensible approach. However, access to the PCR test

is required. Because mupirocin is self-administered, the

patient must be informed about the need for the treatment and the technique of insertion. In the absence of

access to PCR testing, routine prophylaxis with mupirocin is recommended.

IV. Guidelines for Appropriate Dosing of

Prophylactic Antibiotics

RECOMMENDATIONS

1. In patients for whom cefazolin is the appropriate

prophylactic antibiotic for cardiac surgery, administration within 60 minutes of the skin incision is

indicated (Class I, Level of Evidence A). The preoperative prophylactic dose of cefazolin for a patient of greater than 60 kg body weight is recommended to be 2 g (Class I, Level of Evidence B).

Ann Thorac Surg

2007;83:1569 �C76

2. When the surgical incision remains open in the

operating room, to patients with normal renal function, a second dose of 1 g should be administered

every 3 to 4 hours. If it is apparent that cardiopulmonary bypass will be discontinued within 4 hours,

it is appropriate to delay until perfusion is complete

to maximize effective blood levels (Class I, Level of

Evidence B).

3. In patients for whom vancomycin is an appropriate

prophylactic antibiotic for cardiac surgery, a dose of

1 to 1.5 g or a weight-adjusted dose of 15 mg/kg

administered intravenously slowly over 1 hour,

with completion within 1 hour of the skin incision,

is recommended (Class I, Level of Evidence A). A

second dose of vancomycin of 7.5 mg/kg may be

considered during cardiopulmonary bypass, although its usefulness is not well established (Class

IIb, Level of Evidence C).

4. For patients who receive an aminoglycoside (usually gentamicin, 4 mg/kg) in addition to vancomycin before cardiac surgery, the initial dose should

be administered within 1 hour of the skin incision

(Class I, Level of Evidence C). Redosing an aminoglycoside during cardiopulmonary bypass is not

indicated and may be harmful (Class III, Level of

Evidence C).

There is a considerable body of evidence supporting

the need for the timely administration of preoperative

antibiotics, which means administration within 1 hour of

the skin incision [48, 49]. These data accrue from numerous animal and clinical studies and are broadly applicable to all procedures for which prophylactic antibiotics

are administered [50, 51]. In spite of the relative paucity

of controlled randomized or large-scale retrospective

studies to address this issue specifically in cardiac surgery, the timing of the administration of the prophylactic

antibiotic is quite important to the cardiac surgical community. Cardiopulmonary bypass (CPB) is a technique

that is nearly exclusively used by cardiac surgeons, and it

has profound effects on the volume of distribution, and

elimination kinetics of a variety of drugs including the

commonly used prophylactic antibiotics such as cephalosporins, vancomycin, and aminoglycosides [52�C56].

Certain drugs, including opiates, nitrates and vancomycin also have been shown to be sequestered in the

components of the heart lung machine, decreasing biological availability both during and after the completion

of CPB [52, 55]. Therefore, appropriate perioperative

dosing of antibiotics during cardiac surgery presents

unique challenges, particularly since tissue levels, specifically in bone and sternal fat, are likely more relevant

than the more commonly measured serum concentrations. In fact, cefazolin tissue concentrations during surgery are clearly correlated with body weight (increased

body mass index correlates with decreased tissue levels)

such that therapeutic tissue levels may not be achieved in

the morbidly obese patient even with 2 g administered

for prophylaxis [57].

Several studies have investigated intraoperative vancomycin [54 �C56], cephalosporin [53, 58], and aminoglycoside [54, 59] pharmacokinetics. After a single preoperative dose of vancomycin, typically administered over 1

hour, immediately before the skin incision serum concentrations averaged 18 to 66 mg/L after a dose of either

1 g or a weight-adjusted dose of 15 mg/kg [54 �C56]. All of

these studies also documented an 11% to 41% abrupt

decrease in serum vancomycin concentration after the

initiation of cardiopulmonary bypass due primarily to

dilution in direct proportion to the pump prime volume.

During cardiopulmonary bypass, there is a progressive

decline in serum concentrations due to a combination of

renal clearance and sequestration in the heart lung

machine [54 �C56]. After a single preoperative dose, the

serum level in each of the reported studies remains

above the minimal inhibitory concentration (MIC) for

90% of both methicillin-sensitive and methicillinresistant S aureus (1 mg/L) and coagulase-negative Staphylococcus (2 mg/L) throughout the procedure with an

average bypass time of approximately 1 to 2 hours

[54 �C56]. There is incomplete recovery of serum levels

after bypass, however, owing to vancomycin sequestration in the heart-lung machine, alterations in protein

binding, and persistent changes in the volume of distribution after bypass. Similarly, studies have shown that

aminoglycosides [54], first- and second-generation cephalosporins [53, 58] have a similar (as much as 50%)

reduction in serum concentration after the initiation of

CPB.

As a result of the reduction in the levels of cefazolin

and vancomycin immediately after and during CPB, two

studies evaluated the efficacy of administering a second

dose of cefazolin or a second dose of vancomycin after

the initiation of cardiopulmonary bypass [15, 58]. Both

studies found that with the second dosing regimen, the

serum levels were above the MIC for both S aureus and

coagulase-negative Staphylococci throughout the procedure. The two-dose regimen of vancomycin resulted in

higher serum levels but no significant difference in sternal bone, fat, myocardial, or pericardial tissue levels [15].

It is now firmly established with good documentation

from both clinical and experimental studies that readministration of a prophylactic antibiotic during surgery

should be within two half-lives of the antibiotic, exclusive

of any influence of the effects of cardiopulmonary bypass

[48, 60]. Cefazolin has a half-life of approximately 1.8

hours, and therefore it is recommended that there should

be additional dosing during surgery every 3 to 4 hours

when an operation is proceeding with an open wound

beyond that period. The major consideration for defining

the appropriate pharmacodynamics of antimicrobials is

to maintain the serum level of any antibiotic used above

the MIC for the infecting pathogens, presumed in cardiac

surgery to be Staphylococcus sp, while the operative

wound remains open. This typically dictates readministration approximately every two serum half-lives of each

antibiotic considered appropriate [61].

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ANTIBIOTIC PROPHYLAXIS IN CARDIAC SURGERY

1573

V. Guidelines for Prophylactic Antibiotics in

Special Circumstances

Allergy to Penicillin

RECOMMENDATIONS

1. In patients with a history of an immunoglobulin-E

(IgE)�Cmediated reaction to penicillin or cephalosporin (anaphylaxis, hives, or angioedema), vancomycin should be given preoperatively and for no

more than 48 hours. Alternatively, skin testing may

be performed in these patients and, if negative, a

cephalosporin regimen administered (Class I, Level

of Evidence A).

2. For patients with a history of a non-IgE mediated

reaction to penicillin (such as a simple rash) or an

unclear history either vancomycin or a cephalosporin

is recommended for prophylaxis with the understanding that these patients have a low incidence of

significant allergic reactions to cephalosporins (Class

I, Level of Evidence B).

3. The addition of an aminoglycoside or other gramnegative bacterial coverage to a vancomycin antibiotic regimen may be reasonable, but its efficacy is not

well established (Class IIb, Level of Evidence C).

In patients with a history suggestive of an IgEmediated reaction to penicillin (anaphylaxis, hives, or

angioedema), indiscriminate use of a cephalosporin for

surgical prophylaxis in cardiovascular surgery is not

advised [62]. Early studies established a cross-reactivity

rate between penicillin and cephalosporins at approximately 20% [63]. More recent data including those cephalosporins in current clinical use suggests a crossreactivity rate of less than 2% [64].

As many as 20% of the general population are labeled

penicillin-allergic. Fewer than half of these will have a

history suggesting an IgE-mediated reaction to penicillin.

Of these, fewer than 20% will have a positive penicillin

skin-test [65]. Those patients with nonsuggestive or unknown histories have a penicillin skin-test positivity rate

of less than 2% [66]. Among all patients labeled penicillin-allergic, the frequency of serious reactions to cephalosporin administration is less than 1% [64].

With regard to choice of alternative prophylaxis in the

presence of allergy, vancomycin appears to be best owing to

its gram-positive coverage and, particularly, coverage of

methicillin-resistant S aureus. There are concerns over lack

of gram-negative coverage with vancomycin relative to

cephalosporins. For this reason, an aminoglycoside, usually

gentamicin, should be added. It must be recognized, however, that gentamicin is associated with nephrotoxicity and

ototoxicity, and excretion is delayed after cardiopulmonary

bypass [67]. Therefore, a single dose, or at most two doses,

of no more than 4 mg/kg is recommended [67]. There is no

study directly comparing vancomycin and vancomycin plus

an aminoglycoside. A single study from 1987 compared

gentamicin plus a ?-lactam with the latter alone and found

no benefit to the combination therapy, compounded by the

appearance of resistant gram-negative organisms only in

patients receiving gentamicin [13].

MISCELLANEOUS

Ann Thorac Surg

2007;83:1569 �C76

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